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Positron emission tomography (PET) with (15)O tracers provides essential information in patients with cerebral vascular disorders, such as cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen (CMRO(2)). However, most of techniques require an additional C(15)O scan for compensating cerebral blood volume (CBV). We aimed to establish a technique to calculate all functional images only from a single dynamic PET scan, without losing accuracy or statistical certainties. The technique was an extension of previous dual-tracer autoradiography (DARG) approach, but based on the basis function method (DBFM), thus estimating all functional parametric images from a single session of dynamic scan acquired during the sequential administration of H(2)(15)O and (15)O(2). Validity was tested on six monkeys by comparing global OEF by PET with those by arteriovenous blood sampling, and tested feasibility on young healthy subjects. The mean DBFM-derived global OEF was 0.57±0.06 in monkeys, in an agreement with that by the arteriovenous method (0.54±0.06). Image quality was similar and no significant differences were seen from DARG; 3.57%±6.44% and 3.84%±3.42% for CBF, and -2.79%±11.2% and -6.68%±10.5% for CMRO(2). A simulation study demonstrated similar error propagation between DBFM and DARG. The DBFM method enables accurate assessment of CBF and CMRO(2) without additional CBV scan within significantly shortened examination period, in clinical settings.

Positron emission tomography (PET) with [(11)C]raclopride has been used to investigate the density (B(max)) and affinity (K(d)) of dopamine D(2) receptors related to several neurological and psychiatric disorders. However, in assessing the B(max) and K(d), multiple PET scans are necessary under variable specific activities of administered [(11)C]raclopride, resulting in a long study period and unexpected physiological variations. In this paper, we have developed a method of multiple-injection graphical analysis (MI-GA) that provides the B(max) and K(d) values from a single PET scan with three sequential injections of [(11)C]raclopride, and we validated the proposed method by performing numerous simulations and PET studies on monkeys. In the simulations, the three-injection protocol was designed according to prior knowledge of the receptor kinetics, and the errors of B(max) and K(d) estimated by MI-GA were analyzed. Simulations showed that our method could support the calculation of B(max) and K(d), despite a slight overestimation compared with the true magnitudes. In monkey studies, we could calculate the B(max) and K(d) of diseased or normal striatum in a 150 mins scan with the three-injection protocol of [(11)C]raclopride. Estimated B(max) and K(d) values of D(2) receptors in normal or partially dopamine-depleted striatum were comparable to the previously reported values.

Cerebral metabolic rate of oxygen (CMRO(2)) can be assessed quantitatively using (15)O(2) and positron emission tomography. Determining the arterial input function is considered critical with regards to the separation of the metabolic product of (15)O(2) (RW) from a measured whole blood. A mathematical formula based on physiologic model has been proposed to predict RW. This study was intended to verify the adequacy of that model and a simplified procedure applying that model for wide range of species and physiologic conditions. The formula consists of four parameters, including of a production rate of RW (k) corresponding to the total body oxidative metabolism (BMRO(2)). Experiments were performed on 6 monkeys, 3 pigs, 12 rats, and 231 clinical patients, among which the monkeys were studied at varied physiologic conditions. The formula reproduced the observed RW. Greater k values were observed in smaller animals, whereas other parameters did not differ amongst species. The simulation showed CMRO(2) sensitive only to k, but not to others, suggesting that validity of determination of only k from a single blood sample. Also, k was correlated with BMRO(2), suggesting that k can be determined from BMRO(2). The present model and simplified procedure can be used to assess CMRO(2) for a wide range of conditions and species.

The threshold of cerebral blood flow (CBF) into infarction in rats has been indicated to be similar to that in patients. However, CBF does not reflect metabolic function, and so estimations of oxygen metabolism have been required. Here, we estimated changes in oxygen metabolism after occluding the right middle cerebral artery (MCA) in rats using an injectable (15)O-O(2) we developed. A decrease in CBF (left: 0.67+/-0.22 mL/min/g, right: 0.44+/-0.17 mL/min/g, P<0.05) and compensatory increase in the oxygen extraction fraction (OEF) (left: 0.42+/-0.13, right: 0.50+/-0.19, P<0.05) were observed at 1-h after occlusion. In contrast, a marked decrease in CBF and the cerebral metabolic rate for oxygen and a collapse of the compensatory OEF mechanism were found at 24 h after occlusion. Injectable (15)O-O(2) could be used to reliably estimate oxygen metabolism in an infarction rat model with positron emission tomography.